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Biomedical subjects

J M Olmos

Publications and source records attributed to J M Olmos.

At least 19 recordsLinked to original sources
PubMed2006

Osteoprotegerin and bone mass in squamous cell head and neck cancer patients.

Osteoprotegerin (OPG) is considered one of the main regulators of bone remodeling. Various patterns of serum OPG levels have been described in different types of tumors. We undertook this study to determine serum OPG levels in patients with squamous cell head and neck cancer (SCHNC), analyzing their relationship with other metabolic bone parameters and bone mineral density (BMD), as well as the possible influence of chemotherapy. Forty male patients with localized SCHNC were studied, and their results were compared with those of 40 healthy male controls. The type of treatment followed by each patient was noted. Age, weight, height, and lifestyle habits were recorded; and OPG, Ca(2+), intact parathyroid hormone (iPTH), 25-Hydroxyvitamin D (25OHD) and 1,25-Dihydroxyvitamin D (1,25(OH)(2)D), bone alkaline phosphatase, osteocalcin, and serum C-terminal cross-links telopeptide of type I collagen (ICTP) were determined. Dual-energy X-ray absorptiometry BMD at the lumbar spine, femoral neck, and hip was also measured. Serum OPG was higher in patients than in controls (91.7 +/- 25.8 vs. 77.2 +/- 26.3, P = 0.02). ICTP (a bone resorption marker) was 37% higher in patients (P = 0.007). Bone mass was lower in patients at the lumbar spine, femoral neck, and total hip. Lumbar spine Z-score showed a significant progressive decrease in controls, stage I-III patients, and stage IV patients. Logistic regression analysis showed a significant association between the disease and serum OPG levels, the odds ratio per standard deviation increase of this being 1.9 (95% confidence interval 1.1-3.8, P = 0.04) after adjusting for bone mass and ICTP serum levels, as well as for alcohol and smoking history. Adjustment for alcohol intake and tobacco use did not cancel out BMD differences between patients and controls. Patients with SCHNC show increased OPG serum levels, increased bone resorption, and decreased bone mass. The OPG rise appears to be unrelated to the BMD decrease, and the BMD decrease seems to be, at least in part, independent of smoking and drinking habits. No differences in either OPG or BMD were seen between patients with and without chemotherapy. Further studies are needed to clarify the mechanisms responsible for OPG and BMD changes in SCHNC.

Aged↗
PubMed2006

Factors other than glucocorticoids are involved in the osteoblast activity decrease caused by tissue injury.

OBJECTIVE: Serum osteocalcin is a marker of bone formation. The concentration of osteocalcin is decreased with tissue injury. As glucocorticoids are known both to be increased in this situation and to diminish serum osteocalcin, we have hypothesized that they could be involved in this decrease. DESIGN AND PATIENTS: We compared osteocalcin levels in two groups of patients undergoing abdominal surgery, one receiving thiopental, and the other etomidate, a glucocorticoid synthesis blocker. For comparative reasons, another protein decreased by glucocorticoids (osteoprotegerin) was measured in patients anaesthetized with thiopental. MEASUREMENTS: Serum osteocalcin, cortisol and albumin were determined before and over the 24 h following surgery. Serum concentration of osteoprotegerin (OPG) and receptor activator of the nuclear factor kappaB ligand (RANKL) were also determined before and 24 h after surgery in a third group of nine patients who received thiopental for anaesthetic induction. RESULTS: Cortisol levels were increased in the thiopental group, whereas, as expected, were decreased in etomidate patients. However, serum osteocalcin concentration decreased in a similar way in both groups. Serum OPG and RANKL levels were within the normal range at baseline and did not significantly change after surgery. CONCLUSIONS: The decrease in serum osteocalcin induced by tissue injury is independent of the increase in cortisol secretion triggered by the latter. In addition, another pharmacologically proven effect of cortisol on bone metabolism, OPG inhibition, could not be demonstrated in the first 24 h following surgery, in spite of the physiological increase in endogenous cortisol secretion taking place in this period.

Abdomen↗
PubMed2002

Influence of apolipoprotein E polymorphism on plasma vitamin A and vitamin E levels.

BACKGROUND: Plasma concentrations of vitamins A and E are positively correlated with those of concurrent lipids and, on the other hand, lipid levels are influenced by apolipoprotein E polymorphism. Therefore, the effect of this polymorphism on both vitamins was analysed in an adult population. MATERIALS AND METHODS: Subjects were recruited from a working population. Their anthropometric, lifestyle and dietary intake variables and menopausal status were recorded. Their apolipoprotein E phenotype and their plasma vitamins A and E (by high-performance liquid chromatography) and lipid (enzymatically) concentrations were determined after an overnight fast. The associations of the phenotype with vitamins and lipids were studied in men and women separately and controlling for significant covariates. RESULTS: The apolipoprotein E phenotype was associated with the concentrations of total, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol in women, whereas no associations with lipids were found in men. Vitamin A and vitamin E levels were higher in men than in women, but only the difference in the former persisted after lipid adjustment. Apolipoprotein E2 slightly increased vitamin A levels in women, an effect which was still evident with lipid adjustment. Actually, both the apolipoprotein E phenotype and triglyceride were selected as significant predictors of this vitamin by multiple regression. This phenotype did not affect vitamin E levels in either sex. CONCLUSIONS: Lipids do not mediate the effect of gender on vitamin A levels. Apolipoprotein E polymorphism is an independent determinant of vitamin A levels in women. Pending confirmation by others, we propose that enhancement of this vitamin may contribute to the beneficial impact of the epsilon2 allele on human ageing and health.

Adult↗
PubMed2000

Expression of opioid receptors in osteoblast-like MG-63 cells, and effects of different opioid agonists on alkaline phosphatase and osteocalcin secretion by these cells.

We have previously shown that several stressful situations associated with tissue injury determine a decrease in serum osteocalcin concentration. Since reduced osteocalcin production is a marker of decreased osteoblastic activity, this finding could be related to the pathogenesis of osteoporosis secondary to some diseases. Endogenous opioids are involved in stress response. Proenkephalin-derived peptides have been shown to inhibit alkaline phosphatase activity, another marker of bone formation, in the murine cell line ROS-17/2.8. On the other hand, serum osteocalcin has been reported as being low in heroin abusers. We have therefore thought it of interest to study the presence of opioid receptors in the human osteoblast-like cell line MG-63, and to evaluate the effects of different opioid agonists on the secretion of alkaline phosphatase and osteocalcin by these cells. The presence of opioid receptors was studied by means of RT-PCR and immunohistochemistry. RT-PCR studies suggested the presence of specific mRNA for the three types of receptors, and immunohistochemistry clearly showed their occurrence. Osteocalcin synthesis was significantly inhibited by high concentrations of the mu agonists morphine and (D-Ala(2), N-MePhe(4),Gly(5)-ol)-enkephalin although no changes were seen with the delta agonist (D-Ala(2),D-leu(5))-enkephalin. Morphine-induced osteocalcin inhibition was abolished when osteoblastic cells were incubated simultaneously with naloxone, whereas it was potentiated when cells were preincubated with naloxone. None of the opioid agonists modified the secretion of alkaline phosphatase. In conclusion, human osteoblast-like cells MG-63 express the three types of opioid receptors. Endogenous opioids may be involved in the reduction of osteocalcin observed in stressful situations associated with tissue injury.

Alkaline Phosphatase↗
PubMed1999

Apolipoprotein E polymorphism in men and women from a Spanish population: allele frequencies and influence on plasma lipids and apolipoproteins.

UNLABELLED: The apolipoprotein (apo) E phenotype and its influence on plasma lipid and apolipoprotein levels were determined in men and women from a working population of Madrid, Spain. The relative frequencies of alleles epsilon(2), epsilon(3) and epsilon(4) for the study population (n=614) were 0.080, 0.842 and 0.078, respectively. In men, apo E polymorphism was associated with variations in plasma triglyceride and very low-density lipoprotein (VLDL) lipid levels. It was associated with the proportion of apo C-II in VLDL, and explained 5.5% of the variability in the latter parameter. In women apo E polymorphism was associated with the concentrations of plasma cholesterol and low-density lipoprotein (LDL) and high-density lipoprotein (HDL) related variables. The allelic effects were examined taking allele epsilon(3) homozygosity as reference. In men, allele epsilon(2) significantly increased VLDL triglyceride and VLDL cholesterol concentrations, and this was accompanied by an increase of the apo C-II content in these particles. Allele epsilon(4) did not show any significant influence on men's lipoproteins. In women, allele epsilon(2) lowered LDL cholesterol and apo B levels, while allele epsilon(4) increased LDL cholesterol and decreased the concentrations of HDL cholesterol, HDL phospholipid and apo A-I. These effects were essentially maintained after excluding postmenopausal women and oral contraceptive users from the analysis. IN CONCLUSION: (1) the population of Madrid, similar to other Mediterranean populations, exhibits an underexpression of apo E4 compared to the average prevalence in Caucasians, (2) gender interacts with the effects of apo E polymorphism: in women, it influenced LDL and HDL levels, whereas in men it preferentially affected VLDL, and (3) allele epsilon(2) decreased LDL levels in women, while it increased both VLDL lipid levels and apo C-II content in men, but, in contrast to allele epsilon(4), it did not show an impact on HDL in either sex.

Adult↗
PubMed1999

Diagnostic approach to patients with suspected pulmonary embolism: a report from the real world.

This study was carried out to examine the diagnostic approach to patients with suspected pulmonary embolism (PE) in a university hospital. A retrospective case record review of 251 patients with suspected pulmonary embolism was carried out according to a standard protocol, which looked at the utilisation of imaging techniques and compared clinical diagnoses with a standardised diagnosis established according to current recommendations. Isotopic lung scan was the most commonly used technique (73%), followed by leg vein sonography (36%) and contrast venography (31%). Lung arteriography was done in only 7% of patients. Among the 205 patients with a clinical diagnosis of PE, 115 (56%) would be diagnosed as having PE according to the standard criteria, 84 (41%) would be unclassified, and six (3%) would not be regarded as having PE. Among patients who were diagnosed as having PE and received anticoagulant therapy, 32% did not have the diagnosis confirmed by an imaging technique. Most of these had a non-diagnostic lung scan which, despite evidence to the contrary, seemed to be interpreted as confirmation of PE. We conclude that clinicians do not seem to follow current recommendations when approaching patients with suspected PE. In particular, there is an over-reliance on lung scans, and the significance of non-diagnostic scans was often misinterpreted. Arteriography was underused. These results emphasise the need to take measures to implement practice guidelines and to explore the usefulness of newer non-invasive techniques.

Anticoagulants↗
PubMed1999

Etidronate inhibits the production of IL-6 by osteoblast-like cells.

IL-6 is a resorbing cytokine synthesized by osteoblasts and monocytes that has been implicated in the pathogenesis of osteoporosis. Bisphosphonates are well-known antiresorptive drugs, the antiosteoclastic effect of which has been recently suggested to be brought about at least in part through osteoblasts. Based on these facts, we have studied the effect of etidronate on the production of IL-6 by two tumoral cell lines of human osteoblastic phenotype (MG63 and SaOs cells), and by peripheral blood mononuclear cells (PBMC). For comparison, another antiresorptive drug, estradiol, was included in the study. MG63 cells were stimulated with LPS and IL-1 beta, SaOs cells with LPS, IL-1 beta and PMA, and PBMC with LPS and PMA. Etidronate was tested at 10(-7), 10(-6), 10(-5), and 10(-4) M, and 17beta-estradiol was tested at 10(-10), 10(-9), 10(-8), and 10(-7) M. IL-6 was determined in supernatants by an ELISA. No significant effect of either etidronate or estradiol on IL-6 secretion by LPS or PMA-stimulated PBMC was found. However, in osteoblastic-like cells, an inhibition of IL-6 production by etidronate in LPS-stimulated cultures was found. At the highest concentrations tested, IL-6 production values were 58 +/- 9% and 53 +/- 8% of those at base line for MG63 and SaOs cells, respectively. Estradiol did not modify IL-6 secretion under any condition. In conclusion, our study supports the contention that the antiresorptive effect of bisphosphonates may be due in part to a decrease in IL-6 production by osteoblasts.

Cells, Cultured↗
PubMed1998

[Agreement in the clinical diagnosis of pulmonary embolism].

BACKGROUND: The diagnosis of pulmonary embolism (PE) may be a difficult task. The diagnostic performance of imaging techniques is limited and pre-test probability of PE, estimated from basic clinical data, must be taken into consideration to interpret their results. The aim of this study was to evaluate the accuracy and agreement of clinicians in estimating PE probability. PATIENTS AND METHODS: We reviewed the charts of 116 patients admitted to hospital for suspected PE. Basic clinical data (symptoms and signs, arterial blood gases, chest X-ray and EKG) were extracted and given to five clinicians, who were asked to estimate the probability of PE. We determined the inter-clinician agreement and compared their estimates with the final diagnoses. RESULTS: Among patients with a final diagnosis of PE, clinical estimations of PE probability were: high in 63%, intermediate in 21%, and low in 16%. The accuracy of estimates varied between 67 and 80%. Actual PE prevalence was 81% among cases estimated as having high probability and 42% in those considered as low probability. The global inter-clinician agreement rates ranged from 56 to 72%, whereas the average kappa coefficient was 0.44. CONCLUSION: Basic clinical data seem to be more useful to predict PE than to exclude it. The accuracy and agreement between estimates from different clinicians are only moderate.

Humans↗
PubMed1998

1,25-Dihydroxyvitamin D3 receptors in peripheral blood mononuclear cells from patients with renal insufficiency.

A reduced expression of the vitamin D receptor (VDR) in parathyroid glands of uremic animals and humans has been observed. Similar results have been obtained by our own group in peripheral blood mononuclear cells (PBMC) from patients with secondary hyperparathyroidism to chronic renal failure. However, the reasons for these changes are not clear. In the present study, we have investigated the specific uptake of [3H]1,25(OH)2D3 by PBMC of 11 women with advanced chronic renal failure (A-CRF), 6 women with mild-moderate renal insufficiency (M-CRF), and 23 healthy women. The mean dissociation constant (KD) was similar in both groups of patients and in healthy women (A-CRF: 0.7 +/- 0.5 x 10(-10) M; M-CRF: 1.1 +/- 0.9 x 10(-10) M; controls: 1.0 +/- 0.6 x 10(-10) M). However, VDR concentration was significantly decreased in A-CRF (0.8 +/- 0.5 fmol/10(7) cells vs. 2.3 +/- 0.9 fmol/10(7) cells in controls, p < 0.001), whereas no changes were seen in M-CRF (1.7 +/- 0.7 fmol/10(7) cells vs. 2.3 +/- 0.9 fmol/10(7) cells in controls). No correlation was seen between VDR and serum calcitriol or PTH levels, when considering both groups of patients together or separately. Conversely, a significant negative correlation was found between VDR and serum creatinine values when A-CRF and M-CRF were considered altogether (r = -0.63; p < 0.01). Treatment with two different schedules of oral calcitriol (five patients with 0.5 microgram/day for 1 month and four patients with 2 micrograms/day for 7 days) did not change VDR concentrations. We conclude that the low levels of serum 1,25(OH)2D3 of uremia are not responsible for the decrease in VDR concentration found in these patients.

Adult↗
PubMed1998

Seasonal deficiency of vitamin D in children: a potential target for osteoporosis-preventing strategies?

Peak bone mass attained after skeletal growth is a major determinant of the risk of developing osteoporosis later in life, hence the importance of nutritional factors that contribute to bone mass gain during infancy and adolescence. An adequate supply of vitamin D is essential for normal bone homeostasis. This study was undertaken to determine what the levels are of 25-hydroxyvitamin D (25(OH)D) that may be considered desirable in children and to assess if normal children maintain these levels throughout the year. Vitamin D metabolites and parathyroid hormone (PTH) serum levels were measured in 21 children in March and October, prior to and after the administration of a daily supplement of 25(OH)D (40 microg for 7 consecutive days). There were inverse correlations between basal 25(OH)D levels and supplementation-induced changes in serum 1,25(OH)2D (r = 0.57, p < 0.05) and PTH (r = 0.41, p < 0.05). When basal levels of 25(OH)D were below 20 ng/ml, the supplement induced an increase in serum 1,25(OH)2D; with basal 25(OH)D under 10-12 ng/ml, the supplement also decreased serum PTH. The lowest serum level of 25(OH)D in 43 normal children studied in summer was 13 ng/ml. Those results suggested that the lowest limit for desirable levels of 25(OH)D in children was somewhere between 12 and 20 ng/ml. However, 31% of 51 normal children studied in winter had levels below 12 ng/ml, and 80% had levels lower than 20 ng/ml. Those children are likely to have suboptimal bioavailability of vitamin D, which might hamper their achievement of an adequate peak bone mass. Since cutaneous synthesis of vitamin D is rather limited in winter, oral vitamin D supplementation should be considered.

Administration, Oral↗
PubMed1997

[McArdle's disease in adults: clinical and genetic study].

McArdle's disease is a rare metabolic myopathy resulting from an absence of functional muscle glycogen phosphorylase that is inherited as an autosomal recessive condition. Recent molecular genetic studies have identified more than ten different mutations in patients with McArdle's disease, although a nonsense point mutation at codon 49 in exon 1 (R49X) accounts for approximately 85% of mutant alleles in American and British patients. We describe clinical, biochemical and genetic characteristics of five adults patients with McArdle's disease studied at our hospital during the last 10 years.

Adolescent↗
PubMed1997

Bronchiolitis obliterans and IgA nephropathy. A new cause of pulmonary-renal syndrome.

IgA nephropathy is a common form of glomerulonephritis, classically manifested by asymptomatic hematuria. Although the exact pathophysiologic mechanism is still unknown, renal damage has been related to mesangial deposition of IgA-containing immune complexes. In recent years, some lung diseases have been associated with IgA nephropathy, including pulmonary hemorrhage and sarcoidosis. We report a patient with idiopathic bronchiolitis obliterans who developed a rapidly progressive glomerulonephritis due to IgA deposits. Extensive deposits of IgA were also found in the lungs, thus suggesting a pathogenetic role for IgA in tissue injury at both organ levels. To our knowledge this association has not been previously described in the literature.

Aged↗
PubMed1995

Expression and functional role of nitric oxide synthase in osteoblast-like cells.

Nitric oxide synthases (NOS) are enzymes that produce nitric oxide (NO) from L-arginine in a reaction yielding citrulline as a coproduct. Nitric oxide modulates the activity of a wide variety of cells, but little is known about its effects on bone cells. In the present study we report that the NOS inhibitor NG-monomethyl-L-arginine (NMMA) induced a dose-dependent inhibitory effect on the proliferation of the osteoblast-like cell lines MG63 and ROS 17/2.8. The inhibitory effect was prevented by increasing L-arginine concentrations in the medium and by the NO donor sodium nitroprusside. Likewise, NMMA inhibited interleukin-6 secretion, independently of its effect on cell number. NOS expression by MG63 cells was confirmed by measuring their ability to metabolize radiolabeled L-arginine to citrulline. NOS bioactivity was detected in unstimulated cells, but was markedly increased by stimulating the cells with cytokines, lipopolysaccharide, or 1,25-dihydroxyvitamin D3. NOS activity was partially dependent upon the presence of calcium in the medium. Furthermore, constitutive-type NOS (c-NOS) and inducible-type NOS (i-NOS) mRNA expression was detected in ROS 17/2.8 cells after reverse transcription and polymerase chain reaction amplification. In conclusion, osteoblast-like cells express c-NOS and i-NOS, and NOS activity seems to play an important role in the regulation of cell proliferation and function.

Amino Acid Oxidoreductases↗
PubMed1995

Interleukin-4 as a bone regulatory factor: effects on murine osteoblast-like cells.

Bone remodelling is regulated at the local level by an incompletely elucidated cytokine network. In the present study we have determined the effect of interleukin-4 (IL-4), a cytokine produced by T lymphocytes and other cells, on the activity of murine osteoblasts. IL-4 (0.1-10 ng/ml) did not influence the proliferation rate of the osteoblast-like cell line MC3T3, but inhibited the expression of alkaline phosphatase. In long-term cultures supplemented with ascorbic acid and glycerophosphate such an effect was accompanied by a retardation of matrix mineralization. IL-4 also stimulated M-CSF expression by MC3T3 cells, both at the RNA and bioactivity levels. However, no stimulation of IL-1, IL-6, GM-CSF or PGE2 production was observed. An IL-4-induced inhibition of alkaline phosphatase expression and retardation of mineralization was also found in cultures of primary osteoblast-like cells isolated from neonatal mice calvariae. These results suggest that IL-4, probably released by cells within the bone marrow, may locally influence the activity of bone-forming cells.

Alkaline Phosphatase↗